The objective of this research is to study the biochemistry and metabolism of the isolated perfused-ventilated newborn lungs, and to determine what are the initial biochemical changes that result from ventilating these newborn lungs with high oxygen concentrations. Artificial ventilation with high oxygen concentrations is used frequently in the treatment of newborns with respiratory distress, often allowing enough time for the infant to develop sufficient pulmonary function to support himself. However, frequently oxygen therapy is associated with pulmonary lesions in both newborns and adults. Studies to date have not defined the early biochemical changes in alveolar cells produced by oxygen toxicity. My specific goals are: (1) to learn and to develop an isolated perfused ventilated newborn lung technique, (2) to study some baseline metabolic parameters of this preparation, (3) to locate certain biochemical effects of high oxygen concentrations on the perfused ventilated newborn lung, (4) to investigate ways of preventing undesired biochemical changes caused by high oxygen concentrations. Initial studies will establish the perfusion and ventilation conditions for maximal metabolic and histologic survival of the lung in vitro. Secondly, the metabolism of the alveolar cell and the maintenance of the extracellular alveolar lining under standard ventilation will be assessed. Histological and chemical methods will be used to follow the integrity and quantity of the alveolar lining surfactant. Glucose metabolism and enzyme assays, representing various pathways and subcellular particles, will be used to establish cellular function. Next, the effects of high oxygen concentrations on the above processes will be studied. Finally, if detrimental effects of oxygen are detected, attempts would be made to block or slow the process by using biochemical drug-antagonism or induction. Later, it may be possible to adapt the technique to newborn primates and newborn human lungs obtained from stillborns and autopsy material.